Indoles, Indazoles, and Related Analogs for Inhibiting YAP/TAZ-TEAD

Abstract

The present disclosure relates to novel compounds, to said compounds for use as a medicine, more in particular for the prevention or treatment of diseases mediated by activity of YAP/TAZ-TEAD transcription, yet more in particular for the prevention or treatment of cancer or fibrosis. The present disclosure also relates to a method for the prevention or treatment of said diseases comprising the use of the novel compounds.

1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
         or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein: 
         R 1  is selected from the group consisting of:
 (i) hydrogen, 
 (ii) unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of:
 (a) unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of:
 (1) halogen, 
 (2) cyano, 
 (3) C 1 -C 6  alkyl, 
 (4) C 3 -C 6  cycloalkyl, 
 (5) C 1 -C 6  haloalkyl, 
 (6) —OZ 1 , 
 (7) C 2 -C 6  alkenyl, and 
 (8) C 2 -C 6  alkynyl, 
 
 (b) unsubstituted or substituted C 3 -C 6  cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:
 (1) halogen, 
 (2) cyano, 
 (3) C 1 -C 6  alkyl, 
 (4) C 3 -C 6  cycloalkyl, 
 (5) C 1 -C 6  haloalkyl, and 
 (6) —OZ 1 , 
 
 (c) C 2 -C 6  alkynyl, and 
 (d) unsubstituted or substituted C 3 -C 6  heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, C 2 -C 8  alkenyl, and C 1 -C 6  alkyl, 
 
 (iii) unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, 
 (f) —OZ 1 , and 
 (g) unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6  alkyl, and C 1 -C 6  haloalkyl, and —OZ 1 . 
 
 (iv) unsubstituted or substituted 5- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, 
 (f) —OZ 1 , and 
 (g) unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6  alkyl, and C 1 -C 6  haloalkyl, and —OZ 1 , 
 
 (v) unsubstituted or substituted C 3 -C 6  cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, and 
 (f) —OZ 1 , 
 
 (vi) unsubstituted or substituted C 3 -C 6  heterocycle, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, and 
 (f) —OZ 1 , 
 
 (vii) —S(═O) 2 Z 2 , and 
 (viii) —C(═O)Z 2 ; 
 
         Y 1  is selected from the group consisting of ═CR 2 —, ═N—, and —C(═O)—; 
         with the provisos that:
 (i)   represents a double bond when Y 1  is ═CR 2 — or ═N—, and R 4  is absent; or 
 (ii)   represents a single bond when Y 1  is —C(═O)—, and R 4  is selected from the group consisting of hydrogen and C 1 -C 6  alkyl; 
 
       
       R 2  is selected from the group consisting of:
 (i) hydrogen, 
 (ii) C 1 -C 6  alkyl, and 
 (iii) —(CH 2 ) n —NR 5a R 5b ; 
 
       n is 0 or 1; 
       R 5a  is selected from the group consisting of:
 (i) hydrogen, 
 (ii) unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) hydroxy, 
 (c) cyano, 
 (d) —OZ 1 , 
 (e) —SZ 1 , 
 (f) —NZ 3 Z 4 , 
 (g) —C(═O)Z 2    
 (h) C(═O)OH, 
 (i) —C(═O)OZ 2 , 
 (j) —C(═O)NZ 3 Z 4 , 
 (k) —NZ 5 C(═O)Z 2 , 
 (l) —NZ 5 C(═O)OZ 2 , 
 (m) —NZ 5 C(═O)NZ 3 Z 4 , 
 (n) —S(═O) 2 Z 8 , 
 (o) —S(═O) 2 NZ 3 Z 4 , 
 (p) —S(═O)(═NZ 6 )Z 2 , 
 (q) —S(═Z 6 )(═NZ 7 )Z 2 , 
 (r) —S(═O)(═NZ 6 )NZ 3 Z 4 , 
 (s) —NZ 5 S(═O) 2 Z 2 , 
 (t) —NZ 5 S(═O) 2 NZ 3 Z 4 , 
 (u) —NZ 5 S(═O)(═NZ 6 )Z 2 , 
 (v) —NZ 5 S(═NZ 6 )(═NZ 7 )Z 2 , and 
 (w) —NZ 5 S(═O)(═NZ 6 )NZ 3 Z 4 , 
 
 (iii) —C(═O)Z 2    
 (iv) —C(═O)OZ 2 , 
 (v) —C(═O)NZ 3 Z 4 , 
 (vi) —S(═O) 2 Z 8 , 
 (vii) —S(═O) 2 NZ 3 Z 4 , 
 (viii) —S(═O)(═NZ 6 )Z 2 , 
 (xi) —S(═Z 6 )(═NZ 7 )Z 2 , and 
 (x) —S(═O)(═NZ 6 )NZ 3 Z 4 ; 
 
       R 5b  is selected from the group consisting of hydrogen and C 1 -C 6  alkyl; 
       R 3  and R 4  are independently selected from the group consisting of:
 (i) hydrogen, 
 (ii) C 1 -C 6  alkyl, and 
 (iii) —(CH 2 ) p —NR 6a R 6b ; 
 
       p is 0 or 1; 
       R 6a  is selected from the group consisting of:
 (i) hydrogen, 
 (ii) unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) hydroxy, 
 (c) cyano, 
 (d) —OZ 1 , 
 (e) —SZ 1 , 
 (f) —NZ 3 Z 4 , 
 (g) —C(═O)Z 2    
 (h) C(═O)OH, 
 (i) —C(═O)OZ 2 , 
 (j) —C(═O)NZ 3 Z 4 , 
 (k) —NZ 5 C(═O)Z 2 , 
 (l) —NZ 5 C(═O)OZ 2 , 
 (m) —NZ 5 C(═O)NZ 3 Z 4 , 
 (n) —S(═O) 2 Z 8 , 
 (o) —S(═O) 2 NZ 3 Z 4 , 
 (p) —S(═O)(═NZ 6 )Z 2 , 
 (q) —S(═Z 6 )(═NZ 7 )Z 2 , 
 (r) —S(═O)(═NZ 6 )NZ 3 Z 4 , 
 (s) —NZ 5 S(═O) 2 Z 2 , 
 (t) —NZ 5 S(═O) 2 NZ 3 Z 4 , 
 (u) —NZ 5 S(═O)(═NZ 6 )Z 2 , 
 (v) —NZ 5 S(═NZ 6 )(═NZ 7 )Z 2 , 
 (w) —NZ 5 S(═O)(═NZ 6 )NZ 3 Z 4 , and 
 (x) C 2 -C 6  alkenyl 
 
 (iii) —C(═O)Z 2    
 (iv) —C(═O)OZ 2 , 
 (v) —C(═O)NZ 3 Z 4 , 
 (vi) —S(═O) 2 Z 8 , 
 (vii) —S(═O) 2 NZ 3 Z 4 , 
 (viii) —S(═O)(═NZ 6 )Z 2 , 
 (xi) —S(═Z 6 )(═NZ 7 )Z 2 , and 
 (x) —S(═O)(═NZ 6 )NZ 3 Z 4 ; 
 
       R 6b  is selected from the group consisting of hydrogen and C 1 -C 6  alkyl; 
       each Z 1  is independently selected from the group consisting of:
 (i) hydrogen, 
 (ii) unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , C 3 -C 8  cycloalkyl, ——C(═O)OH —S(═O) 2 Z 8 , —NZ 3 Z 4 , 4- to 8-membered heterocycle, 5- to 9-membered heteroaryl, and unsubstituted or substituted aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6  haloalkyl, and cyano, 
 (iii) unsubstituted or substituted C 2 -C 6  alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , halogen and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iv) C 2 -C 6  alkynyl, 
 (v) C 3 -C 6 cycloalkyl, 
 (vi) C 3 -C 6  cycloalkenyl, 
 (vii) C 1 -C 6  haloalkyl, 
 (viii) unsubstituted or substituted 4- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6  alkyl, and C 2 -C 6  alkenyl, and 
 (ix) unsubstituted or substituted aryl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O) 2 Z 8 , —NZ 3 Z 4  and 4- to 8-membered heterocycle; 
 
       each Z 2  is independently selected from the group consisting of:
 (i) C 1 -C 6  alkyl, 
 (ii) unsubstituted or substituted C 2 -C 6  alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , halogen and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iii) C 2 -C 6  alkynyl, 
 (iv) C 3 -C 6  cycloalkyl, 
 (v) C 3 -C 6  cycloalkenyl, and 
 (vi) C 1 -C 6  haloalkyl; 
 
       each Z 3  is independently selected from the group consisting of:
 (i) hydrogen; 
 (ii) unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of C 2 -C 6  alkenyl, cyano, —C(═O)OH, —S(═O) 2 Z 8 , halogen, —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iii) unsubstituted or substituted C 2 -C 6  alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , halogen and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iv) C 2 -C 6  alkynyl, 
 (v) C 3 -C 6  cycloalkyl, 
 (vi) C 3 -C 6  cycloalkenyl, and 
 (vii) C 1 -C 6  haloalkyl; 
 
       each Z 4 , Z 5 , Z 6  and Z 7  is independently selected from the group consisting of:
 (i) hydrogen, 
 (ii) C 1 -C 6  alkyl, and 
 (iii) C 3 -C 6  cycloalkyl; 
 
       each Z 8  is independently selected from the group consisting of:
 (i) hydrogen, 
 (ii) unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, and C 1 -C 6  alkyl, 
 (iii) unsubstituted or substituted C 2 -C 6  alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iv) halogen, and 
 (v) hydroxy; 
 X is selected from the group consisting of ═N— and ═CR 7a —; 
 X 1  is selected from the group consisting of ═N— and ═CR 7b —; 
 X 2  is selected from the group consisting of ═N— and ═CR 7c —; 
 X 3  is selected from the group consisting of ═N— and ═CR 7d —; and 
 R 7a , R 7b , R 7c , and R 7d  is independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, —OZ 1 , and —(CH 2 ) q —NR 6a R 6b ; 
 q is 0 or 1. 
 
     
     
         2 . A compound of Formula II: 
       
         
           
           
               
               
           
         
         or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein: 
         R 1  is selected from the group consisting of:
 (i) hydrogen, 
 (ii) unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of:
 (a) unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of:
 (1) halogen, 
 (2) cyano, 
 (3) C 1 -C 6  alkyl, 
 (4) C 3 -C 6  cycloalkyl, 
 (5) C 1 -C 6  haloalkyl, 
 (6) —OZ 1 , 
 (7) C 2 -C 6  alkenyl, and 
 (8) C 2 -C 6  alkynyl, 
 
 (b) unsubstituted or substituted C 3 -C 6  cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:
 (1) halogen, 
 (2) cyano, 
 (3) C 1 -C 6  alkyl, 
 (4) C 3 -C 6  cycloalkyl, 
 (5) C 1 -C 6  haloalkyl, and 
 (6) —OZ 1 , 
 
 (c) C 2 -C 6  alkynyl, 
 
 (iii) unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, 
 (f) —OZ 1 , and 
 (g) unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6  alkyl, and C 1 -C 6  haloalkyl, and —OZ 1 , 
 
 (iv) unsubstituted or substituted 5- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, 
 (f) —OZ 1 , and 
 (g) unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6  alkyl, and C 1 -C 6  haloalkyl, and —OZ 1 , 
 
 (v) unsubstituted or substituted C 3 -C 6  cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, and 
 (f) —OZ 1 , 
 
 (vi) unsubstituted or substituted C 3 -C 6  heterocycle, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, and 
 (f) —OZ 1 , 
 
 (vii) —S(═O) 2 Z 2 , and 
 (viii) —C(═O)Z 2 ; 
 
         Y 1  is selected from the group consisting of ═CR 2 —, ═N—, and —C(═O)—; 
         with the provisos that:
 (i)   represents a double bond when Y 1  is ═CR 2 — or ═N—, and R 4  is absent; or 
 (ii)   represents a single bond when Y 1  is —C(═O)—, and R 4  is selected from the group consisting of hydrogen and C 1 -C 6  alkyl; 
 
       
       R 2  is selected from the group consisting of:
 (i) hydrogen, 
 (ii) C 1 -C 6  alkyl, and 
 (iii) —(CH 2 ) n —NR 5a R 5b ; 
 
       n is 0 or 1; 
       R 5a  is selected from the group consisting of:
 (i) hydrogen, 
 (ii) unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) hydroxy, 
 (c) cyano, 
 (d) —OZ 1 , 
 (e) —SZ 1 , 
 (f) —NZ 3 Z 4 , 
 (g) —C(═O)Z 2    
 (h) —C(═O)OH, 
 (i) —C(═O)OZ 2 , 
 (j) —C(═O)NZ 3 Z 4 , 
 (k) —NZ 5 C(═O)Z 2 , 
 (l) —NZ 5 C(═O)OZ 2 , 
 (m) —NZ 5 C(═O)NZ 3 Z 4 , 
 (n) —S(═O) 2 Z 8 , 
 (o) —S(═O) 2 NZ 3 Z 4 , 
 (p) —S(═O)(═NZ 6 )Z 2 , 
 (q) —S(═Z 6 )(═NZ 7 )Z 2 , 
 (r) —S(═O)(═NZ 6 )NZ 3 Z 4 , 
 (s) —NZ 5 S(═O) 2 Z 2 , 
 (t) —NZ 5 S(═O) 2 NZ 3 Z 4 , 
 (u) —NZ 5 S(═O)(═NZ 6 )Z 2 , 
 (v) —NZ 5 S(═NZ 6 )(═NZ 7 )Z 2 , and 
 (w) —NZ 5 S(═O)(═NZ 6 )NZ 3 Z 4 , 
 
 (iii) —C(═O)Z 2    
 (iv) —C(═O)OZ 2 , 
 (v) —C(═O)NZ 3 Z 4 , 
 (vi) —S(═O) 2 Z 8 , 
 (vii) —S(═O) 2 NZ 3 Z 4 , 
 (viii) —S(═O)(═NZ 6 )Z 2 , 
 (xi) —S(═Z 6 )(═NZ 7 )Z 2 , and 
 (x) —S(═O)(═NZ 6 )NZ 3 Z 4 ; 
 
       R 5b  is selected from the group consisting of hydrogen and C 1 -C 6  alkyl; 
       R 3  and R 4  are independently selected from the group consisting of:
 (i) hydrogen, 
 (ii) C 1 -C 6  alkyl, and 
 (iii) —(CH 2 ) p —NR 6a R 6b ; 
 
       p is 0 or 1; 
       R 6a  is selected from the group consisting of:
 (i) hydrogen, 
 (ii) unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) hydroxy, 
 (c) cyano, 
 (d) —OZ 1 , 
 (e) —SZ 1 , 
 (f) —NZ 3 Z 4 , 
 (g) —C(═O)Z 2    
 (h) C(═O)OH, 
 (i) —C(═O)OZ 2 , 
 (j) —C(═O)NZ 3 Z 4 , 
 (k) —NZ 5 C(═O)Z 2 , 
 (l) —NZ 5 C(═O)OZ 2 , 
 (m) —NZ 5 C(═O)NZ 3 Z 4 , 
 (n) —S(═O) 2 Z 8 , 
 (o) —S(═O) 2 NZ 3 Z 4 , 
 (p) —S(═O)(═NZ 6 )Z 2 , 
 (q) —S(═Z 6 )(═NZ 7 )Z 2 , 
 (r) —S(═O)(═NZ 6 )NZ 3 Z 4 , 
 (s) —NZ 5 S(═O) 2 Z 2 , 
 (t) —NZ 5 S(═O) 2 NZ 3 Z 4 , 
 (u) —NZ 5 S(═O)(═NZ 6 )Z 2 , 
 (v) —NZ 5 S(═NZ 6 )(═NZ 7 )Z 2 , and 
 (w) —NZ 5 S(═O)(═NZ 6 )NZ 3 Z 4 , 
 
 (iii) —C(═O)Z 2    
 (iv) —C(═O)OZ 2 , 
 (v) —C(═O)NZ 3 Z 4 , 
 (vi) —S(═O) 2 Z 8 , 
 (vii) —S(═O) 2 NZ 3 Z 4 , 
 (viii) —S(═O)(═NZ 6 )Z 2 , 
 (xi) —S(═Z 6 )(═NZ 7 )Z 2 , and 
 (x) —S(═O)(═NZ 6 )NZ 3 Z 4 ; 
 
       R 6b  is selected from the group consisting of hydrogen and C 1 -C 6  alkyl; 
       each Z 1  is independently selected from the group consisting of:
 (i) hydrogen, 
 (ii) C 1 -C 6  alkyl, 
 (iii) unsubstituted or substituted C 2 -C 6  alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , halogen and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iv) C 2 -C 6  alkynyl, 
 (v) C 3 -C 6  cycloalkyl, 
 (vi) C 3 -C 6  cycloalkenyl, and 
 (vii) C 1 -C 6  haloalkyl; 
 
       each Z 2  is independently selected from the group consisting of:
 (i) C 1 -C 6  alkyl, 
 (ii) unsubstituted or substituted C 2 -C 6  alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , halogen and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iii) C 2 -C 6  alkynyl, 
 (iv) C 3 -C 6  cycloalkyl, 
 (v) C 3 -C 6 cycloalkenyl, and 
 (vi) C 1 -C 6  haloalkyl; 
 
       each Z 3  is independently selected from the group consisting of:
 (i) hydrogen; 
 (ii) C 1 -C 6  alkyl, 
 (iii) unsubstituted or substituted C 2 -C 6  alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , halogen and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iv) C 2 -C 6  alkynyl, 
 (v) C 3 -C 6  cycloalkyl, 
 (vi) C 3 -C 6  cycloalkenyl, and 
 (vii) C 1 -C 6  haloalkyl; 
 
       each Z 4 , Z 5 , Z 6  and Z 7  is independently selected from the group consisting of:
 (i) hydrogen, 
 (ii) C 1 -C 6  alkyl, and 
 (iii) C 3 -C 6  cycloalkyl; 
 
       each Z 8  is independently selected from the group consisting of:
 (i) hydrogen, 
 (ii) C 1 -C 6  alkyl, 
 (iii) unsubstituted or substituted C 2 -C 6  alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iv) halogen, and 
 (v) hydroxy; 
 X is selected from the group consisting of ═N— and ═CR 7a —; 
 X 1  is selected from the group consisting of ═N— and ═CR 7b —; 
 X 2  is selected from the group consisting of ═N— and ═CR 7c —; 
 X 3  is selected from the group consisting of ═N— and ═CR 7d —; and 
 R 7a , R 7b , R 7c , and R 7d  is independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, —OZ 1 , and —NZ 3 Z 4 . 
 
     
     
         3 . The compound of  claim 1  or  2  of Formula III: 
       
         
           
           
               
               
           
         
         or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof. 
       
     
     
         4 . The compound of any one of  claims 1 - 3 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:
 R 2  is —(CH 2 ) n —NR 5a R 5b ; and   R 3  is selected from the group consisting of hydrogen and C 1 -C 6  alkyl.   
     
     
         5 . The compound of any one of  claims 1 - 4 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R 5a  is —C(═O)Z 2  and R 5b  is hydrogen. 
     
     
         6 . The compound of any one of  claims 1 - 5 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:
 R 2  is selected from the group consisting of hydrogen and C 1 -C 6  alkyl; and   R 3  is —(CH 2 ) p —NR 6a R 6b .   
     
     
         7 . The compound of any one of  claims 1 - 6 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R 6a  is —C(═O)Z 2  and R 6b  is hydrogen. 
     
     
         8 . The compound of  claim 1  or  2  of Formula IV: 
       
         
           
           
               
               
           
         
         or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof. 
       
     
     
         9 . The compound any one of  claim 1 ,  2 , or  8 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R 3  is —(CH 2 ) p —NR 6a R 6b . 
     
     
         10 . The compound of any one of  claim 1 ,  2 ,  8 , or  9 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:
 R 6a  is selected from the group consisting of —C(═O)Z 2  and —S(═O) 2 Z 8 ; and   R 6b  is hydrogen.   
     
     
         11 . The compound of  claim 1  or  2  of Formula V: 
       
         
           
           
               
               
           
         
         or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof. 
       
     
     
         12 . The compound of any one of  claim 1 ,  2 , or  11 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R 3  is —(CH 2 ) p —NR 6a R 6b . 
     
     
         13 . The compound of any one of  claim 1 ,  2 ,  11 , or  12 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:
 R 6a  is selected from the group consisting of —C(═O)Z 2 ; and   R 6b  is hydrogen.   
     
     
         14 . The compound of any one of  claim 1 ,  2 , or  11 - 13 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R 1  is unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of halogen, hydroxy, cyano, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl, and —OZ 1 . 
     
     
         15 . The compound of any one of  claim 1 ,  2 , or  11 - 14 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:
 X is —CR 7a ═;   X 1  is —CR 7b ═;   X 2  is —CR 7c ═; and   X 3  is —CR 7d ═.   
     
     
         16 . The compound of  claim 1 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, selected from the group consisting of:
 N-[[5-(cyanomethoxy)-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[5-[[rac-tetrahydrofuran-3-yl]methoxy]-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[5-[[(3S)-tetrahydrofuran-3-yl]methoxy]-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[5-[[(3R)-tetrahydrofuran-3-yl]methoxy]-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[5-phenoxy-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[6-(cyclopropoxy)-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[5-(3-methyl-2,6-dioxo-pyrimidin-4-yl)oxy-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[5-benzyloxy-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[5-(1H-pyrazol-3-ylmethoxy)-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[1-[4-(trifluoromethyl)phenyl]pyrazolo[3,4-c]pyridin-3-yl]methyl]prop-2-enamide;   N-[[5-prop-2-ynoxy-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[5-(cyclopropylmethoxy)-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[5-(cyclopropylmethoxy)-1-[4-(trifluoromethyl)phenyl]indazol yl]methyl]methanesulfonamide;   2-[[[1-[4-(trifluoromethyl)phenyl]indazol-3-yl]amino]methyl]prop-2-enoic acid;   N-[[5-(trifluoromethyl)-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide;   N-[[6-(trifluoromethyl)-1-[4-(trifluoromethyl)phenyl]indazol-3-yl]methyl]prop-2-enamide; and   N-[[1-(4,4-difluorocyclohexyl)indazol-3-yl]methyl]prop-2-enamide.   
     
     
         17 . The compound of  claim 2 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, selected from the group consisting of:
 N-(1-(4-(trifluoromethyl)phenyl)-1H-indol-3-yl)acrylamide;   N-(1-(4-(trifluoromethyl)phenyl)-1H-indol-3-yl)acetamide;   N-((1-(4-(trifluoromethyl)phenyl)-1H-indol-3-yl)methyl)acrylamide;   N-((1-(4-(trifluoromethyl)phenyl)-1H-indol-3-yl)methyl)propionamide;   N-(1-phenyl-1H-indol-3-yl)acrylamide;   N-(1-(4-isopropylphenyl)-1H-indol-3-yl)acrylamide;   N-((1-(4-(trifluoromethyl)phenyl)-1H-indol-2-yl)methyl)acrylamide;   N-(1-(4-chlorophenyl)-1H-indol-3-yl)acrylamide;   N-(1-(3-chlorophenyl)-1H-indol-3-yl)acrylamide;   N-(1-([1,1′-biphenyl]-4-yl)-1H-indol-3-yl)acrylamide;   N-((1-(4-(trifluoromethyl)phenyl)-1H-indol-2-yl)methyl)propionamide;   N-((1-(3-(trifluoromethyl)benzyl)-1H-indol-2-yl)methyl)acrylamide;   N-((1-(4-(trifluoromethyl)benzyl)-1H-indol-2-yl)methyl)acrylamide;   N-((1-(4-(trifluoromethyl)phenyl)-1H-indazol-3-yl)methyl)acrylamide;   N-((1-(4-(trifluoromethyl)phenyl)-1H-indazol-3-yl)methyl)methanesulfonamide;   N-(2-oxo-1-(4-(trifluoromethyl)phenyl)indolin-3-yl)acrylamide;   N-(2-oxo-1-(4-(trifluoromethyl)phenyl)indolin-3-yl)acetamide; and   N-((1-(4-(trifluoromethyl)phenyl)-1H-indazol-3-yl)methyl)propionamide.   
     
     
         18 . A compound of Formula VI: 
       
         
           
           
               
               
           
         
         or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein: 
         R 8  is selected from the group consisting of:
 (i) unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of:
 (a) unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of:
 (1) halogen, 
 (2) cyano, 
 (3) C 1 -C 6  alkyl, 
 (4) C 3 -C 6  cycloalkyl, 
 (5) C 1 -C 6  haloalkyl, 
 (6) —OZ 1 , 
 (7) C 2 -C 6  alkenyl, and 
 (8) C 2 -C 6  alkynyl, 
 
 (b) unsubstituted or substituted C 3 -C 6  cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:
 (1) halogen, 
 (2) cyano, 
 (3) C 1 -C 6  alkyl, 
 (4) C 3 -C 6  cycloalkyl, 
 (5) C 1 -C 6  haloalkyl, and 
 (6) —OZ 1 , 
 
 (c) C 2 -C 6  alkynyl, 
 
 (ii) unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, and 
 (f) —OZ 1 , 
 
 (iii) unsubstituted or substituted 5- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, and 
 (f) —OZ 1 , 
 
 (iv) unsubstituted or substituted C 3 -C 6  cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, and 
 (f) —OZ 1 , 
 
 (v) unsubstituted or substituted C 3 -C 6  heterocycle, wherein one or more substituents are independently selected from the group consisting of:
 (a) halogen, 
 (b) cyano, 
 (c) C 1 -C 6  alkyl, 
 (d) C 3 -C 6  cycloalkyl, 
 (e) C 1 -C 6  haloalkyl, and 
 (f) —OZ 1 , 
 
 (vi) —S(═O) 2 Z 2 , and 
 (vii) —C(═O)Z 2 ; 
 
         X is —N(R 11 )—; or X is absent; 
         R 11  is selected from the group consisting of hydrogen and C 1 -C 6  alkyl; 
         R 9  is selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
         R 12  is selected from the group consisting of:
 (i) hydrogen, 
 (ii) unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of:
 (a) unsubstituted or substituted C 6 -C 10  aryl, wherein one or more substituents are independently selected from the group consisting of:
 (1) halogen, 
 (2) cyano, 
 (3) C 1 -C 6  alkyl, 
 (4) C 3 -C 6  cycloalkyl, 
 (5) C 1 -C 6  haloalkyl, 
 (6) —OZ 1 , 
 (7) C 2 -C 6  alkenyl, and 
 (8) C 2 -C 6  alkynyl, 
 
 (b) unsubstituted or substituted C 3 -C 6  cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:
 (1) halogen, 
 (2) cyano, 
 (3) C 1 -C 6  alkyl, 
 (4) C 3 -C 6  cycloalkyl, 
 (5) C 1 -C 6  haloalkyl, and 
 (6) —OZ 1 , and 
 
 (c) unsubstituted or substituted 5- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of:
 (1) halogen, 
 (2) cyano, 
 (3) C 1 -C 6  alkyl, 
 (4) C 3 -C 6  cycloalkyl, 
 (5) C 1 -C 6  haloalkyl, and 
 (6) —OZ 1 , and 
 
 
 (iii) C 1 -C 6  haloalkyl; 
 
         R 10  is —(CH 2 ) q —C(═O)R 13    
         q is 0, 1, or 2; 
         R 13  is selected from the group consisting of —OH, OZ 1 , and —NZ 3 Z 4 ; 
       
       each Z 1  is independently selected from the group consisting of:
 (i) hydrogen, 
 (ii) C 1 -C 6  alkyl, 
 (iii) unsubstituted or substituted C 2 -C 6  alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , halogen and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iv) C 2 -C 6  alkynyl, 
 (v) C 3 -C 6  cycloalkyl, 
 (vi) C 3 -C 6  cycloalkenyl, and 
 (vii) C 1 -C 6  haloalkyl; 
 
       each Z 2  is independently selected from the group consisting of:
 (i) C 1 -C 6  alkyl, 
 (ii) unsubstituted or substituted C 2 -C 6  alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , halogen and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iii) C 2 -C 6  alkynyl, 
 (iv) C 3 -C 6  cycloalkyl, 
 (v) C 3 -C 6  cycloalkenyl, and 
 (vi) C 1 -C 6  haloalkyl; 
 
       each Z 3  is independently selected from the group consisting of:
 (i) hydrogen; 
 (ii) C 1 -C 6  alkyl, 
 (iii) unsubstituted or substituted C 2 -C 6  alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , halogen and unsubstituted or substituted C 1 -C 6  alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 8 , —NZ 3 Z 4  and 4- to 8-membered heterocycle, 
 (iv) C 2 -C 6  alkynyl, 
 (v) C 3 -C 6  cycloalkyl, 
 (vi) C 3 -C 6  cycloalkenyl, and 
 (vii) C 1 -C 6  haloalkyl; and 
 
       each Z 4  is independently selected from the group consisting of:
 (i) halogen, 
 (ii) C 1 -C 6  alkyl, and 
 (iii) C 3 -C 6  cycloalkyl. 
 
     
     
         19 . The compound of  claim 18 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, selected from the group consisting of:
 2-(8-(1-methyl-1H-pyrazol-3-yl)-6-phenylimidazo[1,2-a]pyridin-2-yl)acetic acid;   N-methyl-2-(8-(1-methyl-1H-pyrazol-3-yl)-6-phenylimidazo[1,2-a]pyridin-2-yl)acetamide;   2-(6-phenyl-8-(1-(pyridin-3-ylmethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-2-yl)acetic acid;   2-(8-(1-methyl-1H-pyrazol-3-yl)-6-(phenylamino)imidazo[1,2-a]pyridin-2-yl)acetic acid; and   N-methyl-2-(8-(1-methyl-1H-pyrazol-3-yl)-6-(phenylamino)imidazo[1,2-a]pyridin-2-yl)acetamide.   
     
     
         20 . A pharmaceutical composition comprising the compound of any one of  claims 1 - 19 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, and a pharmaceutically acceptable carrier. 
     
     
         21 . The compound of any one of  claims 1 - 19 , or the pharmaceutical composition of  claim 20 , for use as a medicine. 
     
     
         22 . The compound of any one of  claims 1 - 19 , or the pharmaceutical composition of  claim 20 , for use in the prevention or treatment of a YAP/TAZ-TEAD activation mediated disorder in an animal, mammal or human. 
     
     
         23 . The compound of any one of  claims 1 - 19 , or the pharmaceutical composition of  claim 20 , for use in the prevention or treatment of a YAP/TAZ-TEAD activation mediated disorders is selected from the group comprising cancer, fibrosis and YAP/TAZ-TEAD activation mediated congenital disorders. 
     
     
         24 . The compound of any one of  claims 1 - 19 , or the pharmaceutical composition of  claim 20 , for use in the prevention or treatment of a YAP/TAZ-TEAD activation mediated disorder selected from lung cancer, breast cancer, head and neck cancer, oesophageal cancer, kidney cancer, bladder cancer, colon cancer, ovarian cancer, cervical cancer, endometrial cancer, liver cancer (including but not limited to cholangiocarcinoma), skin cancer, pancreatic cancer, gastric cancer, brain cancer and prostate cancer, mesotheliomas, and/or sarcomas. 
     
     
         25 . The compound of any one of  claims 1 - 19 , or the pharmaceutical composition of  claim 20 , for use in the prevention or treatment of a YAP/TAZ-TEAD activation mediated disorders selected from acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bronchogenic carcinoma, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin's and non-Hodgkin's), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom's macroglobulinemia, testicular tumors, uterine cancer and Wilms' tumor. 
     
     
         26 . A method for the prevention or treatment of a YAP/TAZ-TEAD activation mediated disorders in an animal, mammal or human comprising administering to said animal, mammal or human in need for such prevention or treatment an effective dose of the compounds of any one of  claims 1 - 19 . 
     
     
         27 . A method of treatment or prevention of YAP/TAZ-TEAD activation mediated disorder according to  claim 26  to a patient in need thereof in combination with one or more other medicines selected from the group consisting of EGFR inhibitors, MEK inhibitors, AXL inhibitors, B-RAF inhibitors, and RAS inhibitors.